Publications by authors named "Giovanna Calandra-Buonaura"

96 Publications

Premotor antidepressants use differs according to Parkinson's disease subtype: A cohort study.

Parkinsonism Relat Disord 2021 May 6;87:137-141. Epub 2021 May 6.

IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy. Electronic address:

Background: Depression is more frequently associated with akinetic-rigid/postural instability gait difficulty subtypes of Parkinson's disease than with tremor-dominant subtype.

Objectives: The aim of the study is to investigate the frequency of exposure to antidepressant drugs, as proxy of depression, before motor onset according to Parkinson's disease subtypes.

Method: Based on a historical cohort design, the exposure to antidepressant drugs before Parkinson's disease motor onset was obtained from the drug prescription database and assessed in the resident population of the Local Healthcare Trust of Bologna (443,117 subjects older than 35 years). Diagnosis of Parkinson's disease and subtype (tremor dominant, non-tremor dominant) at onset were recorded by neurologists and obtained from the "ParkLink Bologna" record linkage system. Exposure to antidepressants was compared both to the general population and between the two subtypes.

Results: From 2006 to 2018, 198 patients had a tremor dominant subtype at onset whereas 450 did not. Comparison with the general population for antidepressant exposure showed an adjusted hazard ratio of 0.86 (95% CI 0.44-1.70) for the tremor dominant subtype and 1.66 (1.16-2.39) for the non-tremor dominant subtype. Comparison of non-tremor dominant with tremor dominant subtypes showed an adjusted odds ratio of 1.86 (1.05-3.95) for antidepressant exposure.

Conclusions: In our study, non-tremor dominant Parkinson's disease at onset was significantly associated with exposure to antidepressants in comparison to the general population and in comparison with the tremor dominant subtype. These results support the hypothesis of different biological substrates for different Parkinson's disease subtypes even before motor onset.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.023DOI Listing
May 2021

Functional motor phenotypes: to lump or to split?

J Neurol 2021 May 7. Epub 2021 May 7.

IRCCS Mondino Foundation, Pavia, Italy.

Introduction: Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms.

Objective: To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities.

Methods: Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted.

Results: A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors.

Conclusions: Our data support the evidence of a large overlap between FMD phenotypes.
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http://dx.doi.org/10.1007/s00415-021-10583-wDOI Listing
May 2021

Dysphagia in multiple system atrophy consensus statement on diagnosis, prognosis and treatment.

Parkinsonism Relat Disord 2021 May 30;86:124-132. Epub 2021 Mar 30.

Department of Neurology, New York University School of Medicine, New York, NY, USA. Electronic address:

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure plus cerebellar syndrome and/or parkinsonism. Dysphagia is a frequent and disabling symptom in MSA and its occurrence within 5 years of motor onset is an additional diagnostic feature. Dysphagia can lead to aspiration pneumonia, a recognized cause of death in MSA. Guidelines for diagnosis and management of dysphagia in MSA are lacking. An International Consensus Conference among experts with methodological support was convened in Bologna to reach consensus statements for the diagnosis, prognosis, and treatment of dysphagia in MSA. Abnormalities of the oral and pharyngeal phases of swallowing, esophageal dysfunction and aspiration occur in MSA and worsen as the disease progresses. According to the consensus, dysphagia should be investigated through available screening questionnaires and clinical and instrumental assessment (videofluoroscopic study or fiberoptic endoscopic evaluation of swallowing and manometry) at the time of MSA diagnosis and periodically thereafter. There is evidence that dysphagia is associated with poor survival in MSA, however effective treatments for dysphagia are lacking. Compensatory strategies like diet modification, swallowing maneuvers and head postures should be applied and botulinum toxin injection may be effective in specific conditions. Percutaneous endoscopic gastrostomy may be performed when there is a severe risk of malnutrition and pulmonary complications, but its impact on survival is undetermined. Several research gaps and unmet needs for research involving diagnosis, prognosis, and treatment were identified.
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http://dx.doi.org/10.1016/j.parkreldis.2021.03.027DOI Listing
May 2021

Persistence of Facio-Skeletal Myorhythmia During Sleep in anti-IgLON5 Disease.

Mov Disord Clin Pract 2021 Apr 25;8(3):460-463. Epub 2021 Feb 25.

IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica Rete Metropolitana NEUROMET Bologna Italy.

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http://dx.doi.org/10.1002/mdc3.13159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015885PMC
April 2021

Quantitative Assessment of Motor Response to a Low Subacute Levodopa Dose in the Differential Diagnosis of Parkinsonisms at Disease Onset: Data from the BoProPark Cohort.

J Parkinsons Dis 2021 ;11(2):811-819

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Background: Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs) may be difficult at disease onset. The response to levodopa (LD) is a key supportive feature but its definition is largely empirical. Studies evaluating this issue by quantitative tests are scanty.

Objective: We aimed to assess the utility of a subacute low LD dose kinetic-dynamic test in the differential diagnosis between PD and APs. It was applied at the baseline of a prospective follow-up in patients with parkinsonian signs within three years of disease motor onset ("BoProPark" cohort) and eventually diagnosed as PD or APs according to consensus criteria.

Methods: Patients under at least 3-month LD therapy received a first morning fasting dose of LD/benserazide or carbidopa (100/25 mg) and underwent simultaneous serial assessments of plasma LD concentration and alternate finger tapping frequency up to 3 h. The main outcome was the extent of LD motor response, calculated by the area under the 3 h tapping effect-time curve (AUC_ETap). A receiver operating characteristic (ROC) curve analysis was performed to establish the optimal AUC_ETap cut-off to differentiate PD and APs.

Results: The first 100 consecutive "BoProPark" patients were analyzed. Forty-seven patients were classified as possible, 37 as probable PD and 16 as APs. AUC_ETap medians were similar in the PD subgroups but reduced to a third in APs (p < 0.001). The optimal AUC_ETap cut-off value was >2186 [(tap/min) x min], with a sensitivity of 92% and a specificity of 75%. Accuracy of the test was 0.85 (95% CI 0.74-0.95), p < 0.0001.

Conclusion: The estimation of 3 h AUC_ETap after a subacute low LD dose proved a reliable, objective tool to assess LD motor response in our cohort of patients. AUC_ETap value rounded to ≥2200 supports PD diagnosis, while lower values may alert to AP diagnoses.
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http://dx.doi.org/10.3233/JPD-202262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150440PMC
January 2021

A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project.

Mech Ageing Dev 2021 03 29;194:111426. Epub 2020 Dec 29.

Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Florence, Italy.

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project "PROPAG-AGEING", whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development.
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http://dx.doi.org/10.1016/j.mad.2020.111426DOI Listing
March 2021

Cognitive Profile and Its Evolution in a Cohort of Multiple System Atrophy Patients.

Front Neurol 2020 23;11:537360. Epub 2020 Nov 23.

IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Cognitive decline is not a characteristic feature of multiple system atrophy (MSA), but recent evidence suggests cognitive impairment as an integral part of the disease. We aim to describe the cognitive profile and its progression in a cohort of patients with MSA. We retrospectively selected patients referred to our department with a clinical diagnosis of MSA who were evaluated at least once a year during the course of the disease and underwent a comprehensive neuropsychological evaluation. At the first evaluation (T0), 37 out of 60 patients (62%) were cognitively impaired, mainly (76%) in attention and executive functioning. Thirteen patients were impaired in one cognitive domain and 24 in more than one cognitive domain. Six out of the 24 had dementia. Twenty patients underwent a follow-up evaluation (T1) after a mean of 16.6 ± 9.3 months from the first evaluation (T0). Eight out of 20 patients were cognitively normal at both T0 and T1. Seven out of 12 patients presented with stable cognitive impairment at T1, while cognitive decline progressed in five patients. Patients with progression in cognitive decline performed significantly worse at T0 than cognitively stable patients. Education was significantly different between patients with and without cognitive impairment. No other differences in demographic and clinical variables and autonomic or sleep disturbances were found. Patients with dementia were older at disease onset and at T0 and had lower education and disease duration at T0 compared to those in other groups. In patients with MSA, we observed three different cognitive profiles: normal cognition, stable selective attention-executive deficits, and progressive cognitive deficits evolving to dementia. The detection of cognitive impairment in patients with suspected MSA suggests the need for comprehensive and longitudinal neuropsychological evaluation.
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http://dx.doi.org/10.3389/fneur.2020.537360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719742PMC
November 2020

Performing sleep studies after the COVID-19 outbreak: practical suggestions from Bologna's sleep unit.

Sleep Med 2021 01 7;77:45-50. Epub 2020 Nov 7.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.

The Coronavirus Disease 2019 (COVID-19) pandemic required a thorough re-organization of every sector of the healthcare system. Sleep laboratories need to renew protocols in order to guarantee the safety of patients and healthcare staff while providing exams. Polysomnography (PSG) examinations are essential for the diagnosis and treatment management of several sleep disorders, which may constitute a public or personal safety issue such as obstructive sleep apnea syndrome. Here we provide some practical advice on how to perform sleep studies after the COVID-19 outbreak based on our experience, the review of the existing literature and current national and international recommendations by Health Authorities. We believe that with appropriate precautions it is possible to guarantee a safe restart of PSG and other sleep studies.
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http://dx.doi.org/10.1016/j.sleep.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837108PMC
January 2021

Functional motor disorders associated with other neurological diseases: Beyond the boundaries of "organic" neurology.

Eur J Neurol 2021 May 2;28(5):1752-1758. Epub 2021 Jan 2.

Movement Disorder Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background And Purpose: The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs").

Methods: For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables).

Results: Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities.

Conclusions: Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.
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http://dx.doi.org/10.1111/ene.14674DOI Listing
May 2021

Risk of Hospitalization and Death for COVID-19 in People with Parkinson's Disease or Parkinsonism.

Mov Disord 2021 01 2;36(1):1-10. Epub 2020 Dec 2.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Background: The risk of COVID-19 and related death in people with Parkinson's disease or parkinsonism is uncertain. The aim of the study was to assess the risk of hospitalization for COVID-19 and death in a cohort of patients with Parkinson's disease or parkinsonism compared with a control population cohort, during the epidemic bout (March-May 2020) in Bologna, northern Italy.

Methods: Participants of the ParkLink study with the clinical diagnosis of Parkinson's disease or parkinsonism and people anonymously matched (ratio 1:10) for sex, age, district, and Charlson Index were included. The hospital admission rate for COVID-19 (February 26-May 31, 2020) and the death rate for any cause were the outcomes of interest.

Results: The ParkLink cohort included 696 subjects with Parkinson's disease and 184 with parkinsonism, and the control cohort had 8590 subjects. The 3-month hospitalization rate for COVID-19 was 0.6% in Parkinson's disease, 3.3% in parkinsonism, and 0.7% in controls. The adjusted hazard ratio (age, sex, district, Charlson Index) was 0.8 (95% CI, 0.3-2.3, P = 0.74) in Parkinson's disease and 3.3 (1.4-7.6, P = 0.006) in parkinsonism compared with controls. Twenty-nine of the infected subjects died; 30-day fatality rate was 35.1%, without difference among the 3 groups. Six of 10 Parkinson's disease/parkinsonism patients had the infection during hospitalization or in a nursing home.

Conclusions: Parkinson's disease per se probably is not a risk factor for COVID-19 hospitalization. Conversely, parkinsonism is an independent risk factor probably because of a more severe health status, entailing higher care dependence and placement in high-infection-risk accommodations. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753472PMC
January 2021

Validation of the new index of baroreflex function to identify neurogenic orthostatic hypotension.

Auton Neurosci 2020 12 7;229:102744. Epub 2020 Nov 7.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica NeuroMet, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.

Background: According to expert opinion, orthostatic hypotension (OH) associated to a change in heart rate (ΔHR) less than 15 bpm suggests neurogenic OH (NOH). Recently, the ratio between HR and systolic blood pressure changes at 3 min of tilt test (ΔHR/ΔSBP) has been proposed as a better index than the ΔHR cut-off of 17 bpm. Our aim was to validate these indexes based on HR in an independent cohort of patients who performed cardiovascular reflex tests according to standardized procedures at our Institution.

Methods: We applied the HR indexes to all cardiovascular reflex tests that fulfilled the following criteria: (1) presence of classical OH at tilt test, (2) reliable Valsalva manoeuvre (VM), (3) absence of heart disease. We classified OH according to VM (absence of overshoot = NOH), and verified how many were correctly identified by ΔHR/ΔSBP (≤0.49 neurogenic) and ΔHR (≤17 and ≤15 neurogenic).

Results: We identified 369 tests with OH. Based on VM, 335 were NOH. The ΔHR/ΔSBP ≤ 0.49 identified NOH with a sensitivity of 91% and a specificity of 59%, the ΔHR ≤ 17 bpm with 88% sensitivity and 38% specificity, and the ΔHR ≤ 15 bpm with 84% sensitivity and 50% specificity.

Conclusion: In our cohort, the ΔHR/ΔSBP ratio had a good sensitivity but a limited specificity to identify NOH. This easily applicable test may represent a valuable screening tool in a clinical setting to identify patients who need further detailed autonomic testing to confirm the neurogenic origin of OH.
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http://dx.doi.org/10.1016/j.autneu.2020.102744DOI Listing
December 2020

Levodopa/Carbidopa Intestinal Gel Long-Term Outcome in Parkinson's Disease: Focus on Dyskinesia.

Mov Disord Clin Pract 2020 Nov 18;7(8):930-939. Epub 2020 Sep 18.

Department of Neuroscience "Rita Levi Montalcini" University of Torino Turin Italy.

Background: Levodopa-carbidopa intestinal gel (LCIG) treatment has shown variable effect on dyskinesia in Parkinson's disease (PD).

Objective: To identify PD patients who are likely to have troublesome dyskinesia under LCIG treatment and describe the pharmacokinetic-dynamic profile and dyskinesia phenomenology of those patients.

Methods: PD patients were assessed for clinical and therapeutic variables, before LCIG treatment () and at last outpatient visit (). Sub-groups of patients with and without "troublesome dyskinesia" (UPDRS IV, item 33 ≥2), matched for disease and LCIG treatment duration, underwent a pharmacokinetic-dynamic assessment.

Results: We included 53 PD patients. After a mean of 51.7 ± 34.1 months of LCIG treatment, "off-time" was significantly reduced, whereas, dyskinesia duration/disability did not change. The multivariate regression model, adjusted for LCIG treatment duration, showed that being female increases the risk of presenting troublesome dyskinesia at (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 2.4-37.4) that was also significantly associated to longer off periods at (OR= 4.4; 95% CI = 1.1-14.3). Female patients showed a higher risk for a higher dyskinesia score at (sum of the items 32 and 33: = 0.001). Patients with troublesome dyskinesia showed a tendency for a lower motor benefit and the appearance of more severe dyskinesia despite similar levodopa plasma concentration.

Conclusion: Dyskinesia should be carefully monitored in patients undergoing LCIG, with particular caution for female patients. Whether combined clinical and pharmacodynamic assessments could be helpful to manage patients with troublesome dyskinesia under LCIG treatment needs further evaluation in a larger group of patients.
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http://dx.doi.org/10.1002/mdc3.13068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604637PMC
November 2020

Clinical Correlates of Functional Motor Disorders: An Italian Multicenter Study.

Mov Disord Clin Pract 2020 Nov 22;7(8):920-929. Epub 2020 Sep 22.

Department of Systems Medicine University of Rome Tor Vergata Rome Italy.

Background: Functional motor disorders (FMDs) are abnormal movements that are significantly altered by distractive maneuvers and are incongruent with movement disorders seen in typical neurological diseases.

Objective: The objectives of this article are to (1) describe the clinical manifestations of FMDs, including nonmotor symptoms and occurrence of other functional neurological disorders (FND); and (2) to report the frequency of isolated and combined FMDs and their relationship with demographic and clinical variables.

Methods: For this multicenter, observational study, we enrolled consecutive outpatients with a definite diagnosis of FMDs attending 25 tertiary movement disorders centers in Italy. Each patient underwent a detailed clinical evaluation with a definition of the phenotype and number of FMDs (isolated, combined) and an assessment of associated neurological and psychiatric symptoms.

Results: Of 410 FMDs (71% females; mean age, 47 ± 16.1 years) the most common phenotypes were weakness and tremor. People with FMDs had higher educational levels than the general population and frequent nonmotor symptoms, especially anxiety, fatigue, and pain. Almost half of the patients with FMDs had other FNDs, such as sensory symptoms, nonepileptic seizures, and visual symptoms. Patients with combined FMDs showed a higher burden of nonmotor symptoms and more frequent FNDs. Multivariate regression analysis showed that a diagnosis of combined FMDs was more likely to be delivered by a movement disorders neurologist. Also, FMD duration, pain, insomnia, diagnosis of somatoform disease, and treatment with antipsychotics were all significantly associated with combined FMDs.

Conclusions: Our findings highlight the need for multidimensional assessments in patients with FMDs given the high frequency of nonmotor symptoms and other FNDs, especially in patients with combined FMDs.
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http://dx.doi.org/10.1002/mdc3.13077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604660PMC
November 2020

Comparison of 123I-MIBG scintigraphy and phosphorylated α-synuclein skin deposits in synucleinopathies.

Parkinsonism Relat Disord 2020 12 8;81:48-53. Epub 2020 Oct 8.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.

Introduction: Cardiac [123I]metaiodobenzylguanidine scintigraphy (123I-MIBG) is considered a useful test in differentiating multiple system atrophy (MSA) and Lewy body disorders (LBD), including idiopathic Parkinson's disease (IPD), dementia with Lewy bodies (DLB) and pure autonomic failure (PAF). The detection of skin nerve phosphorylated α-synuclein (p-α-syn) deposits could be an alternative marker in vivo. We sought to compare 123I-MIBG scintigraphy and skin biopsy findings in α-synucleinopathies.

Methods: We studied 54 patients (7 DLB, 21 IPD, 13 PAF, 13 MSA) who underwent 123I-MIBG scintigraphy and skin biopsy to evaluate cardiac innervation and skin p-α-syn deposition, respectively.

Results: Cardiac denervation was observed in 90.5% IPD, 100% DLB and PAF and in none of the MSA patients (P < 0.0001) whereas p-α-syn deposits were detected in all DLB and PAF, in 95.2% of IPD and 69.2% of MSA patients (P = 0.02). However, the analysis of skin structures disclosed a different distribution of the deposits in somatic subepidermal plexus and autonomic fibers among groups, showing that p-α-syn deposits rarely affected the autonomic fibers in MSA as opposed to LBD. Studying the p-α-syn deposition in autonomic nerves, concordance among I123-MIBG scintigraphy and skin biopsy results was observed in 100% of DLB and PAF, 95.2% IPD and 92.3% MSA patients. I123-MIBG scintigraphy and autonomic p-α-syn deposits analysis both showed a sensitivity of 97.5% and a specificity of 100% and 92.3%, respectively, in distinguishing LBD and MSA.

Conclusion: Skin biopsy and 123-MIBG scintigraphy can be considered alternative tests for the differential diagnosis of IPD, PAF and DLB versus MSA.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.016DOI Listing
December 2020

Circadian and state-dependent core body temperature in people with spinal cord injury.

Spinal Cord 2021 May 17;59(5):538-546. Epub 2020 Jul 17.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica NeuroMet, Bologna, Italy.

Study Design: Prospective cohort study.

Objectives: To analyze the circadian rhythm and state-dependent modulation of core body temperature (Tcore) in individuals with spinal cord injury (SCI) under controlled environmental conditions.

Setting: Institute of the Neurological Sciences of Bologna, Italy.

Methods: We assessed 48-h rectal Tcore and sleep-wake cycle by means of video-polygraphic recording in five cervical SCI (cSCI), seven thoracic SCI (tSCI), and seven healthy controls under controlled environmental conditions.

Results: cSCI showed higher night-time Tcore values with reduced nocturnal decrease, higher MESOR and earlier acrophase compared with tSCI and controls (p < 0.05 in all comparisons). The mean Tcore values during wake and non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages were higher in cSCI compared with tSCI and controls (p < 0.05). Tcore variability throughout the 24 h differed significantly between cSCI, tSCI, and controls.

Conclusions: cSCI had higher Tcore values without physiological night-time fall compared with controls and tSCI, and a disrupted Tcore circadian rhythm. Furthermore, SCI individuals did not display the physiological state-dependent Tcore modulation. The disconnection of the sympathetic nervous system from its central control caused by the SCI could affect thermoregulation including Tcore modulation during sleep. It is also possible that the reduced representation of deep sleep in people with SCI impairs such ability. Further studies are necessary to evaluate whether improvement of sleep could ameliorate thermoregulation and vice versa.
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http://dx.doi.org/10.1038/s41393-020-0521-8DOI Listing
May 2021

Testing cardiovascular autonomic function in the COVID-19 era: lessons from Bologna's Autonomic Unit.

Clin Auton Res 2020 08 13;30(4):325-330. Epub 2020 Jul 13.

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica NeuroMet, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.

The coronavirus disease 2019 (COVID-19) pandemic has changed the way most medical procedures are performed. Autonomic units, as well as other healthcare sectors, are required to undergo a thorough reorganization of the protocols in order to guarantee the safety of patients and healthcare staff. Cardiovascular autonomic function testing (CAFT) is necessary in certain situations; however, it poses several concerns which need to be addressed. Here, we provide some practical advice based on current national and international health authorities' recommendations and our experience about how to perform CAFT during the COVID-19 emergency. We examine aspects regarding patients, healthcare staff, laboratory preparation, and test performance.
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http://dx.doi.org/10.1007/s10286-020-00710-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355131PMC
August 2020

Should We Consider Deep Brain Stimulation Discontinuation in Late-Stage Parkinson's Disease?

Mov Disord 2020 08 25;35(8):1379-1387. Epub 2020 May 25.

Department of Neuroscience "Rita Levi Montalcini,", University of Torino, Turin, Italy.

Background: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered.

Methods: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment.

Results: Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred.

Conclusions: The vast majority of late-stage PD patients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28091DOI Listing
August 2020

Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies.

Acta Neuropathol 2020 07 27;140(1):49-62. Epub 2020 Apr 27.

IRCCS, Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy.

The clinical diagnosis of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), is challenging, especially at an early disease stage, due to the heterogeneous and often non-specific clinical manifestations. The discovery of reliable specific markers for synucleinopathies would consequently be of great aid to the diagnosis and management of these disorders. Real-Time Quaking-Induced Conversion (RT-QuIC) is an ultrasensitive technique that has been previously used to detect self-templating amyloidogenic proteins in the cerebrospinal fluid (CSF) and other biospecimens in prion disease and synucleinopathies. Using a wild-type recombinant α-synuclein as a substrate, we applied RT-QuIC to a large cohort of 439 CSF samples from clinically well-characterized, or post-mortem verified patients with parkinsonism or dementia. Of significance, we also studied patients with isolated REM sleep behavior disorder (iRBD) (n = 18) and pure autonomic failure (PAF) (n = 28), representing clinical syndromes that are often caused by a synucleinopathy, and may precede the appearance of parkinsonism or cognitive decline. The results show that our RT-QuIC assay can accurately detect α-synuclein seeding activity across the spectrum of Lewy Body (LB)-related disorders (LBD), including DLB, PD, iRBD, and PAF, with an overall sensitivity of 95.3%. In contrast, all but two patients with MSA showed no α-synuclein seeding activity in the applied experimental setting. The analysis of the fluorescence response reflecting the amount of α-synuclein seeds revealed no significant differences between the clinical syndromes associated with LB pathology. Finally, the assay demonstrated 98% specificity in a neuropathological cohort of 101 cases lacking LB pathology. In conclusion, α-synuclein RT-QuIC provides an accurate marker of synucleinopathies linked to LB pathology and may have a pivotal role in the early discrimination and management of affected patients. The finding of no α-synuclein seeding activity in MSA seems to support the current view that MSA and LBD are associated with different conformational strains of α-synuclein.
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http://dx.doi.org/10.1007/s00401-020-02160-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299922PMC
July 2020

Progression and prognosis in multiple system atrophy presenting with REM behavior disorder.

Neurology 2020 04 31;94(17):e1828-e1834. Epub 2020 Mar 31.

From IRCCS Istituto delle Scienze Neurologiche di Bologna (G.G., F.P., A.C., G.B., F.M., P.G., P.C., G.C.-B.), UOC Clinica Neurologica Rete Metropolitana NEUROMET; Department of Biomedical and NeuroMotor Sciences (DiBiNeM) (G.G., V.M., F.P., A.D., G.B., P.C., G.C.-B.), Alma Mater Studiorum-University of Bologna; and Neurology Outpatient Clinic, Department of Primary Care (P.G.), Local Health Authority of Modena, Italy.

Objectives: To investigate (1) the prevalence of REM sleep behavior disorder (RBD) as mode of disease onset in a cohort of patients with multiple system atrophy (MSA) and (2) disease progression and prognosis in patients with MSA with RBD predating (pre-RBD) and following (post-RBD) disease onset.

Methods: We retrospectively identified all patients with a clinical diagnosis of MSA evaluated at least once a year during the disease course. Type of onset was defined by the first reported motor or autonomic symptom/sign related to MSA. The occurrence of symptoms/signs and milestone of disease progression, and their latency from disease onset, were collected. Survival data were calculated. RBD was confirmed by video-polysomnography.

Results: Of a total of 158 patients, pre-RBD represented the mode of disease onset in 27% of patients, preceding disease onset according to the international criteria with a median of 3 (2-5) years. Comparing pre-RBD and post-RBD patients, the first group showed an increased prevalence of autonomic onset of disease, a reduced prevalence of parkinsonism, an earlier onset of stridor, pyramidal signs, symptomatic orthostatic hypotension, urinary dysfunction, severe dysphagia, and wheelchair dependency. The risk of death was higher in patients with pre-RBD.

Conclusions: In our MSA cohort, RBD represented the most frequent mode of disease presentation. A more rapid progression of disease was observed in the pre-RBD group. These findings suggested a careful assessment of sleep disorders to early recognize RBD and a closer follow-up of autonomic dysfunction and stridor in patients with pre-RBD.
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http://dx.doi.org/10.1212/WNL.0000000000009372DOI Listing
April 2020

The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark): study design and population.

Neurol Sci 2020 Sep 26;41(9):2531-2537. Epub 2020 Mar 26.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura 3, 40139, Bologna, Italy.

Objective: The Bologna motor and non-motor prospective study on parkinsonism at onset (BoProPark) was designed to prospectively characterize motor and non-motor features in patients with a progressive neurodegenerative disease starting with parkinsonism since early disease stage and to investigate their diagnostic and prognostic role in the differential diagnosis of Parkinson's disease from atypical parkinsonisms. The aim of this paper is to describe the method and population of the BoProPark study.

Methods: Patients referred to our Department with parkinsonism within 3 years from motor onset were recruited. Secondary causes of parkinsonism were excluded. Each patient underwent a comprehensive evaluation of motor and non-motor symptoms, assessed by means of quantitative, objective instrumental tests in addition to scales and questionnaires. The evaluations were performed at enrolment (T0), after 16 months (T1) and after 5 years (T2). Diagnoses were made according to consensus criteria.

Results: We recruited 150 patients, with mean age 61.5 ± 9.8 years and mean disease duration 20 ± 9 months. H&Y stage was 1 in 47.3% and 2 in 46.7% of cases. Mean UPDRS-III was 17.7 ± 9.2. Fifty-four patients were on dopaminergic treatment with median levodopa equivalent daily dose (LEDD) of 200 mg.

Conclusions: We expect that the prospective nature of the BoProPark study as well as the comprehensive, instrumental evaluation of motor and non-motor symptoms in patients with parkinsonism will provide important new insights for both clinical practice and research. Our data could be used for comparison with other cohorts and shared with national and international collaborators to develop new innovative projects.
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http://dx.doi.org/10.1007/s10072-020-04305-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419369PMC
September 2020

Mathematical modeling and parameter estimation of levodopa motor response in patients with parkinson disease.

PLoS One 2020 3;15(3):e0229729. Epub 2020 Mar 3.

IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Parkinson disease (PD) is characterized by a clear beneficial motor response to levodopa (LD) treatment. However, with disease progression and longer LD exposure, drug-related motor fluctuations usually occur. Recognition of the individual relationship between LD concentration and its effect may be difficult, due to the complexity and variability of the mechanisms involved. This work proposes an innovative procedure for the automatic estimation of LD pharmacokinetics and pharmacodynamics parameters, by a biologically-inspired mathematical model. An original issue, compared with previous similar studies, is that the model comprises not only a compartmental description of LD pharmacokinetics in plasma and its effect on the striatal neurons, but also a neurocomputational model of basal ganglia action selection. Parameter estimation was achieved on 26 patients (13 with stable and 13 with fluctuating LD response) to mimic plasma LD concentration and alternate finger tapping frequency along four hours after LD administration, automatically minimizing a cost function of the difference between simulated and clinical data points. Results show that individual data can be satisfactorily simulated in all patients and that significant differences exist in the estimated parameters between the two groups. Specifically, the drug removal rate from the effect compartment, and the Hill coefficient of the concentration-effect relationship were significantly higher in the fluctuating than in the stable group. The model, with individualized parameters, may be used to reach a deeper comprehension of the PD mechanisms, mimic the effect of medication, and, based on the predicted neural responses, plan the correct management and design innovative therapeutic procedures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229729PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053720PMC
June 2020

Autonomic impairment in sleep: An introduction to the special edition.

Auton Neurosci 2020 03 16;224:102638. Epub 2020 Jan 16.

Department of Neurology, New York University.

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http://dx.doi.org/10.1016/j.autneu.2020.102638DOI Listing
March 2020

Assessing Synergy/Redundancy of Baroreflex and Non-Baroreflex Components of the Cardiac Control during Sleep.

Annu Int Conf IEEE Eng Med Biol Soc 2019 07;2019:4953-4956

Cardiovascular regulation and autonomic function change across sleep stages and compared to wake. Little information is present in literature about cardiac control during sleep especially in relation to new information-theoretic quantities such as synergy and redundancy. In the present work we compute synergy and redundancy of baroreflex and non-baroreflex components of the cardiac control according to two information-theoretic approaches, namely predictive information decomposition (PID) and minimal mutual information (MMI) methods. We applied a bivariate approach to heart period (HP) and systolic arterial pressure (SAP) beat-to-beat variability series during sleep in a healthy subject. PID approach computes the net balance between synergy and redundancy, while MMI calculates the two quantities as separate entities. Results suggested that: i) redundancy was dominant over synergy during NREM phases; ii) redundancy increased during NREM phase; iii) synergy did not change across the sleep stages. We interpret this result as a consequence of the vagal enhancement, slowing and deepening of respiration during NREM phases. These preliminary findings support the potential of assessing redundancy/synergy of baroreflex-related and unrelated regulations during sleep to improve our knowledge about physiological mechanisms.
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http://dx.doi.org/10.1109/EMBC.2019.8856887DOI Listing
July 2019

Stridor in multiple system atrophy: Consensus statement on diagnosis, prognosis, and treatment.

Neurology 2019 10;93(14):630-639

From the IRCCS (P.C., G.C.-B., G.G., F.P., L.V.), Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie (P.C., G.C.-B., G.G., P.M., F.P.), Università di Bologna, Bologna, Italy; Department of Neurology (E.E.B., P.A.L.), Mayo Clinic, Rochester, MN; Multidisciplinary Sleep Unit (A.I.), Neurology Service, Hospital Clinic de Barcelona, IDIBAPS CIBERNED, Barcelona, Spain; UCL Queen Square Institute of Neurology (N.Q.), Queen Square, London; Parkinson's Disease and Movement Disorders Unit (E.T.), Neurology Service, Hospital Clinic de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (E.T.), University of Barcelona (UB), and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain; Department of Neurology (G.K.W.), Innsbruck Medical University, Innsbruck, Austria; Department of Neuroscience (G.A.), Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy; The Multiple System Atrophy Coalition, Inc. (P.B.), Charlotte, NC; Neurophysiopathology Unit (E.A.), IRCCS "C. Mondino" Foundation, Pavia, Italy; Department of Clinical Neurophysiology (I.G.), CHU de Bordeaux, Bordeaux, France; Université de Bordeaux (I.G.), Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Bordeaux, France; CNRS (I.G.), Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, Bordeaux, France; Department of Neurology (T.O.), Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami Uonuma, Niigata, Japan; Parkinson's Disease and Movement Disorders Unit (C.P., N.G.P.), IRCCS "C. Mondino" Foundation, Pavia; Dipartimento di Medicina Specialistica (C.V.), Diagnostica e Sperimentale (DIMES), University of Bologna, Bologna, Italy; Dipartimento di Scienze biomediche e chirurgico specialistiche (C.V.), University of Ferrara, Ferrara, Italy; Department of Neurosciences (A.A.), University of Padua, Padua, Italy; Department of Clinical and Motor Neuroscience (A.P.B.), UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London; Spinal Unit (J.B.), Montecatone Rehabilitation Institute, Imola, Italy; Department of Neurology (H.K.), New York University School of Medicine, New York, NY; Department of Medicine (M.T.P.), Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy; "Luigi Sacco" Department of Biomedical and Clinical Sciences (N.P., A.S.), University of Milan, Milan, Italy; Service de Neurologie (F.T., W.G.M.), CRMR Atrophie Multisystématisée, CHU Bordeaux, Bordeaux, France; Univ. de Bordeaux (F.T., W.G.M.), Institut des Maladies Neurodégénératives, Bordeaux, France; and Department Medicine (W.G.M.), University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a combination of autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor is an additional feature for MSA diagnosis, showing a high diagnostic positive predictive value, and its early occurrence might contribute to shorten survival. A consensus definition of stridor in MSA is lacking, and disagreement persists about its diagnosis, prognosis, and treatment. An International Consensus Conference among experts with methodological support was convened in Bologna in 2017 to define stridor in MSA and to reach consensus statements for the diagnosis, prognosis, and treatment. Stridor was defined as a strained, high-pitched, harsh respiratory sound, mainly inspiratory, occurring only during sleep or during both sleep and wakefulness, and caused by laryngeal dysfunction leading to narrowing of the rima glottidis. According to the consensus, stridor may be recognized clinically by the physician if present at the time of examination, with the help of a witness, or by listening to an audio recording. Laryngoscopy is suggested to exclude mechanical lesions or functional vocal cord abnormalities related to different neurologic conditions. If the suspicion of stridor needs confirmation, drug-induced sleep endoscopy or video polysomnography may be useful. The impact of stridor on survival and quality of life remains uncertain. Continuous positive airway pressure and tracheostomy are both suggested as symptomatic treatment of stridor, but whether they improve survival is uncertain. Several research gaps emerged involving diagnosis, prognosis, and treatment. Unmet needs for research were identified.
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http://dx.doi.org/10.1212/WNL.0000000000008208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814413PMC
October 2019

A New Integrative Theory of Brain-Body-Ecosystem Medicine: From the Hippocratic Holistic View of Medicine to Our Modern Society.

Int J Environ Res Public Health 2019 08 28;16(17). Epub 2019 Aug 28.

Department of Biomedical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Humans are increasingly aware that their fate will depend on the wisdom they apply in interacting with the ecosystem. Its health is defined as the condition in which the ecosystem can deliver and continuously renew its fundamental services. A healthy ecosystem allows optimal interactions between humans and the other biotic/abiotic components, and only in a healthy ecosystem can humans survive and efficiently reproduce. Thus, both the human and ecosystem health should be considered together in view of their interdependence. The present article suggests that this relationship could be considered starting from the Hippocrates (460 BC-370 BC) work "On Airs, Waters, and Places" to derive useful medical and philosophical implications for medicine which is indeed a topic that involves scientific as well as philosophical concepts that implicate a background broader than the human body. The brain-body-ecosystem medicine is proposed as a new more complete approach to safeguarding human health. Epidemiological data demonstrate that exploitation of the environment resulting in ecosystem damage affects human health and in several instances these diseases can be detected by modifications in the heart-brain interactions that can be diagnosed through the analysis of changes in heart rate variability.
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http://dx.doi.org/10.3390/ijerph16173136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747255PMC
August 2019

Use of antidepressants and the risk of Parkinson's disease in the Local Health Trust of Bologna: A historical cohort study.

J Neurol Sci 2019 Oct 7;405:116421. Epub 2019 Aug 7.

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Background: Depression is considered one of the prodromal symptoms of Parkinson's disease (PD) along with sleep disorders, hyposmia and constipation. Prodromal symptoms refer to the stage wherein early motor symptoms and signs allowing a diagnosis of PD are not yet present. The objective of this study was to investigate the association between the use of antidepressants, as indirect measure of depression, and subsequent PD onset, clinically diagnosed, in the Local Health Trust of Bologna, Italy.

Methods: Historical cohort study with use of antidepressants as exposure and PD onset as outcome. The cohort considered consisted of inhabitants of Bologna aged ≥35 years in 2005; those who had used antidepressants in the previous 3 years were excluded. Subjects were followed up from 2006 and until PD onset, migration out of Bologna, death or end of the study period (2017), whichever came first. "The ParkLink Bologna" system was used to detect disease onset. "ParkLink Bologna" is a research study including patients with a clinical diagnosis of PD residing in Bologna. Residents that used antidepressants for at least 180 consecutive days within 1 year were considered exposed. Hazard ratios (HR) and 95% confidence interval (CI) were estimated with Cox proportional hazards models, using exposure as time-dependent variable and adjusting for potential confounders: age, gender, use of medical care and comorbidities.

Results: From 2006 to 2017 199,093 person-years were exposed and 4,286,470 not exposed. Fifty-one subjects with PD were identified in the exposed group and 556 subjects in the non-exposed showing an association of adjusted HR = 1.7 (CI 1.3-2.3). The association was stronger for males (HR 2.2, CI 1.5-3.2) compared to females (HR 1.2, CI 0.8-1.9), for subjects ≤65 years of age (HR 2.4, CI 1.6-3.6) vs. >65 years (HR 1.3, CI 0.8-1.9) and for those with less comorbidities. Age and gender were confounders in the associations between antidepressant use and PD onset.

Conclusions: The use of antidepressants as indirect measure of depression is associated with the subsequent development of PD. Our findings confirm that depression may precede the onset of motor symptoms in PD. The association is stronger for younger subjects, who are males and with fewer comorbidities.
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http://dx.doi.org/10.1016/j.jns.2019.08.006DOI Listing
October 2019

L-Dopa Modulation of Brain Connectivity in Parkinson's Disease Patients: A Pilot EEG-fMRI Study.

Front Neurosci 2019 14;13:611. Epub 2019 Jun 14.

Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.

Studies of functional neurosurgery and electroencephalography in Parkinson's disease have demonstrated abnormally synchronous activity between basal ganglia and motor cortex. Functional neuroimaging studies investigated brain dysfunction during motor task or resting state and primarily have shown altered patterns of activation and connectivity for motor areas. L-dopa administration relatively normalized these functional alterations. The aim of this pilot study was to examine the effects of L-dopa administration on functional connectivity in early-stage PD, as revealed by simultaneous recording of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) data. Six patients with diagnosis of probable PD underwent EEG-fMRI acquisitions (1.5 T MR scanner and 64-channel cap) before and immediately after the intake of L-dopa. Regions of interest in the primary motor and sensorimotor regions were used for resting state fMRI analysis. From the EEG data, weighted partial directed coherence was computed in the inverse space after the removal of gradient and cardioballistic artifacts. fMRI results showed that the intake of L-dopa increased functional connectivity within the sensorimotor network, and between motor areas and both attention and default mode networks. EEG connectivity among regions of the motor network did not change significantly, while regions of the default mode network showed a strong tendency to increase their outflow toward the rest of the brain. This pilot study provided a first insight into the potentiality of simultaneous EEG-fMRI acquisitions in PD patients, showing for both techniques the analogous direction of increased connectivity after L-dopa intake, mainly involving motor, dorsal attention and default mode networks.
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http://dx.doi.org/10.3389/fnins.2019.00611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587436PMC
June 2019

A2A-D2 Heteromers on Striatal Astrocytes: Biochemical and Biophysical Evidence.

Int J Mol Sci 2019 May 17;20(10). Epub 2019 May 17.

Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.

Our previous findings indicate that A2A and D2 receptors are co-expressed on adult rat striatal astrocytes and on the astrocyte processes, and that A2A-D2 receptor⁻receptor interaction can control the release of glutamate from the processes. Functional evidence suggests that the receptor⁻receptor interaction was based on heteromerization of native A2A and D2 receptors at the plasma membrane of striatal astrocyte processes. We here provide biochemical and biophysical evidence confirming that receptor⁻receptor interaction between A2A and D2 receptors at the astrocyte plasma membrane is based on A2A-D2 heteromerization. To our knowledge, this is the first direct demonstration of the ability of native A2A and D2 receptors to heteromerize on glial cells. As striatal astrocytes are recognized to be involved in Parkinson's pathophysiology, the findings that adenosine A2A and dopamine D2 receptors can form A2A-D2 heteromers on the astrocytes in the striatum (and that these heteromers can play roles in the control of the striatal glutamatergic transmission) may shed light on the molecular mechanisms involved in the pathogenesis of the disease.
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http://dx.doi.org/10.3390/ijms20102457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566402PMC
May 2019

Management of supine hypertension in patients with neurogenic orthostatic hypotension: scientific statement of the American Autonomic Society, European Federation of Autonomic Societies, and the European Society of Hypertension.

J Hypertens 2019 08;37(8):1541-1546

Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

: Supine hypertension commonly occurs in patients with neurogenic orthostatic hypotension due to autonomic failure. Supine hypertension promotes nocturnal sodium excretion and orthostatic hypotension, thus, interfering with quality of life. Perusal of the literature on essential hypertension and smaller scale investigations in autonomic failure patients also suggest that supine hypertension may predispose to cardiovascular and renal disease. These reasons provide a rationale for treating supine hypertension. Yet, treatment of supine hypertension, be it through nonpharmacological or pharmacological approaches, may exacerbate orthostatic hypotension when patients get up during the night. Fall-related complications may occur. More research is needed to define the magnitude of the deleterious effects of supine hypertension on cardiovascular, cerebrovascular, and renal morbidity and mortality. Integration of more precise cardiovascular risk assessment, efficacy, and safety data, and the prognosis of the underlying condition causing autonomic failure is required for individualized management recommendations.
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http://dx.doi.org/10.1097/HJH.0000000000002078DOI Listing
August 2019